Exploring Radiotherapy Targeting Strategy and Dose: A Pooled Analysis of Cooperative Group Trials of Combined Modality Therapy for Stage III NSCLC

Steven E. Schild, Herbert H. Pang, Wen Fan, Thomas E. Stinchcombe, Everett E. Vokes, Suresh S. Ramalingam, Jeffrey D. Bradley, Karen Kelly, Xiaofei Wang

Research output: Contribution to journalArticle

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Abstract

Introduction: Concurrent chemoradiotherapy (CRT) is standard therapy for locally advanced NSCLC (LA-NSCLC) patients. This study was performed to examine thoracic radiotherapy (TRT) parameters and their impact on patient survival. Methods: We collected individual patient data from 3600 LA-NSCLC patients participating in 16 cooperative group trials of concurrent CRT. The primary TRT parameters examined included field design strategy (elective nodal irradiation [ENI] compared to involved-field TRT (IF-TRT)), total dose, and biologically effective dose (BED). Hazard ratios (HRs) for overall survival were calculated with univariable and multivariable Cox models. Results: TRT doses ranged from 60 Gy to 74 Gy with most treatments administered once-daily. ENI was associated with poorer survival than IF-TRT (univariable HR = 1.37, 95% confidence interval [CI]: 1.24–1.51, p < 0.0001; multivariable HR = 1.31, 95% CI: 1.08–1.59, p = 0.002). The median survival times of the IF and ENI patients were 24 months and 16 months, respectively. Patients were divided into three dose groups: low total dose (60 Gy), medium total dose (>60 Gy to 66 Gy), and high total dose (>66 Gy to 74 Gy). With reference to the low-dose group, the multivariable HRs were 1.08 for the medium-dose group (95% CI: 0.93–1.25) and 1.12 for the high-dose group (95% CI: 0.97–1.30).The univariate p = 0.054 and multivariable p = 0.17. BED was grouped as follows: low (<55.5 Gy10), medium (55.5 Gy10), or high (>55.5 Gy10). With reference to the low-BED group, the HR was 1.00 (95% CI: 0.85–1.18) for the medium-BED group and 1.10 (95% CI: 0.93–1.31) for the high-BED group. The univariable p = 0.076 and multivariable p = 0.16. Conclusions: For LA-NSCLC patients treated with concurrent CRT, IF-TRT was associated with significantly better survival than ENI-TRT. TRT total and BED dose levels were not significantly associated with patient survival. Future progress will require research focusing on better systemic therapy and TRT.

Original languageEnglish (US)
JournalJournal of Thoracic Oncology
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Combined Modality Therapy
Radiotherapy
Thorax
Confidence Intervals
Chemoradiotherapy
Survival
Proportional Hazards Models
Therapeutics
Research

Keywords

  • Combined modality therapy
  • Locally advanced non-small cell lung cancer
  • Radiation dose
  • Radiation fields
  • Radiotherapy
  • Treatment planning

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Exploring Radiotherapy Targeting Strategy and Dose : A Pooled Analysis of Cooperative Group Trials of Combined Modality Therapy for Stage III NSCLC. / Schild, Steven E.; Pang, Herbert H.; Fan, Wen; Stinchcombe, Thomas E.; Vokes, Everett E.; Ramalingam, Suresh S.; Bradley, Jeffrey D.; Kelly, Karen; Wang, Xiaofei.

In: Journal of Thoracic Oncology, 01.01.2018.

Research output: Contribution to journalArticle

Schild, Steven E. ; Pang, Herbert H. ; Fan, Wen ; Stinchcombe, Thomas E. ; Vokes, Everett E. ; Ramalingam, Suresh S. ; Bradley, Jeffrey D. ; Kelly, Karen ; Wang, Xiaofei. / Exploring Radiotherapy Targeting Strategy and Dose : A Pooled Analysis of Cooperative Group Trials of Combined Modality Therapy for Stage III NSCLC. In: Journal of Thoracic Oncology. 2018.
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title = "Exploring Radiotherapy Targeting Strategy and Dose: A Pooled Analysis of Cooperative Group Trials of Combined Modality Therapy for Stage III NSCLC",
abstract = "Introduction: Concurrent chemoradiotherapy (CRT) is standard therapy for locally advanced NSCLC (LA-NSCLC) patients. This study was performed to examine thoracic radiotherapy (TRT) parameters and their impact on patient survival. Methods: We collected individual patient data from 3600 LA-NSCLC patients participating in 16 cooperative group trials of concurrent CRT. The primary TRT parameters examined included field design strategy (elective nodal irradiation [ENI] compared to involved-field TRT (IF-TRT)), total dose, and biologically effective dose (BED). Hazard ratios (HRs) for overall survival were calculated with univariable and multivariable Cox models. Results: TRT doses ranged from 60 Gy to 74 Gy with most treatments administered once-daily. ENI was associated with poorer survival than IF-TRT (univariable HR = 1.37, 95{\%} confidence interval [CI]: 1.24–1.51, p < 0.0001; multivariable HR = 1.31, 95{\%} CI: 1.08–1.59, p = 0.002). The median survival times of the IF and ENI patients were 24 months and 16 months, respectively. Patients were divided into three dose groups: low total dose (60 Gy), medium total dose (>60 Gy to 66 Gy), and high total dose (>66 Gy to 74 Gy). With reference to the low-dose group, the multivariable HRs were 1.08 for the medium-dose group (95{\%} CI: 0.93–1.25) and 1.12 for the high-dose group (95{\%} CI: 0.97–1.30).The univariate p = 0.054 and multivariable p = 0.17. BED was grouped as follows: low (<55.5 Gy10), medium (55.5 Gy10), or high (>55.5 Gy10). With reference to the low-BED group, the HR was 1.00 (95{\%} CI: 0.85–1.18) for the medium-BED group and 1.10 (95{\%} CI: 0.93–1.31) for the high-BED group. The univariable p = 0.076 and multivariable p = 0.16. Conclusions: For LA-NSCLC patients treated with concurrent CRT, IF-TRT was associated with significantly better survival than ENI-TRT. TRT total and BED dose levels were not significantly associated with patient survival. Future progress will require research focusing on better systemic therapy and TRT.",
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author = "Schild, {Steven E.} and Pang, {Herbert H.} and Wen Fan and Stinchcombe, {Thomas E.} and Vokes, {Everett E.} and Ramalingam, {Suresh S.} and Bradley, {Jeffrey D.} and Karen Kelly and Xiaofei Wang",
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T2 - A Pooled Analysis of Cooperative Group Trials of Combined Modality Therapy for Stage III NSCLC

AU - Schild, Steven E.

AU - Pang, Herbert H.

AU - Fan, Wen

AU - Stinchcombe, Thomas E.

AU - Vokes, Everett E.

AU - Ramalingam, Suresh S.

AU - Bradley, Jeffrey D.

AU - Kelly, Karen

AU - Wang, Xiaofei

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Introduction: Concurrent chemoradiotherapy (CRT) is standard therapy for locally advanced NSCLC (LA-NSCLC) patients. This study was performed to examine thoracic radiotherapy (TRT) parameters and their impact on patient survival. Methods: We collected individual patient data from 3600 LA-NSCLC patients participating in 16 cooperative group trials of concurrent CRT. The primary TRT parameters examined included field design strategy (elective nodal irradiation [ENI] compared to involved-field TRT (IF-TRT)), total dose, and biologically effective dose (BED). Hazard ratios (HRs) for overall survival were calculated with univariable and multivariable Cox models. Results: TRT doses ranged from 60 Gy to 74 Gy with most treatments administered once-daily. ENI was associated with poorer survival than IF-TRT (univariable HR = 1.37, 95% confidence interval [CI]: 1.24–1.51, p < 0.0001; multivariable HR = 1.31, 95% CI: 1.08–1.59, p = 0.002). The median survival times of the IF and ENI patients were 24 months and 16 months, respectively. Patients were divided into three dose groups: low total dose (60 Gy), medium total dose (>60 Gy to 66 Gy), and high total dose (>66 Gy to 74 Gy). With reference to the low-dose group, the multivariable HRs were 1.08 for the medium-dose group (95% CI: 0.93–1.25) and 1.12 for the high-dose group (95% CI: 0.97–1.30).The univariate p = 0.054 and multivariable p = 0.17. BED was grouped as follows: low (<55.5 Gy10), medium (55.5 Gy10), or high (>55.5 Gy10). With reference to the low-BED group, the HR was 1.00 (95% CI: 0.85–1.18) for the medium-BED group and 1.10 (95% CI: 0.93–1.31) for the high-BED group. The univariable p = 0.076 and multivariable p = 0.16. Conclusions: For LA-NSCLC patients treated with concurrent CRT, IF-TRT was associated with significantly better survival than ENI-TRT. TRT total and BED dose levels were not significantly associated with patient survival. Future progress will require research focusing on better systemic therapy and TRT.

AB - Introduction: Concurrent chemoradiotherapy (CRT) is standard therapy for locally advanced NSCLC (LA-NSCLC) patients. This study was performed to examine thoracic radiotherapy (TRT) parameters and their impact on patient survival. Methods: We collected individual patient data from 3600 LA-NSCLC patients participating in 16 cooperative group trials of concurrent CRT. The primary TRT parameters examined included field design strategy (elective nodal irradiation [ENI] compared to involved-field TRT (IF-TRT)), total dose, and biologically effective dose (BED). Hazard ratios (HRs) for overall survival were calculated with univariable and multivariable Cox models. Results: TRT doses ranged from 60 Gy to 74 Gy with most treatments administered once-daily. ENI was associated with poorer survival than IF-TRT (univariable HR = 1.37, 95% confidence interval [CI]: 1.24–1.51, p < 0.0001; multivariable HR = 1.31, 95% CI: 1.08–1.59, p = 0.002). The median survival times of the IF and ENI patients were 24 months and 16 months, respectively. Patients were divided into three dose groups: low total dose (60 Gy), medium total dose (>60 Gy to 66 Gy), and high total dose (>66 Gy to 74 Gy). With reference to the low-dose group, the multivariable HRs were 1.08 for the medium-dose group (95% CI: 0.93–1.25) and 1.12 for the high-dose group (95% CI: 0.97–1.30).The univariate p = 0.054 and multivariable p = 0.17. BED was grouped as follows: low (<55.5 Gy10), medium (55.5 Gy10), or high (>55.5 Gy10). With reference to the low-BED group, the HR was 1.00 (95% CI: 0.85–1.18) for the medium-BED group and 1.10 (95% CI: 0.93–1.31) for the high-BED group. The univariable p = 0.076 and multivariable p = 0.16. Conclusions: For LA-NSCLC patients treated with concurrent CRT, IF-TRT was associated with significantly better survival than ENI-TRT. TRT total and BED dose levels were not significantly associated with patient survival. Future progress will require research focusing on better systemic therapy and TRT.

KW - Combined modality therapy

KW - Locally advanced non-small cell lung cancer

KW - Radiation dose

KW - Radiation fields

KW - Radiotherapy

KW - Treatment planning

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